In their native habitat, 30-50% of African green monkeys have antibodies reactive to simian immunodeficiency virus (SIV). However, Caribbean green monkeys are SIV negative. Although some macaques in captivity are found with SIV and AIDS, macaques in their native habitat of asia examined to date have also been SIV negative. Both human and non-human primate lentiviruses are know to be genetically divergent among individual HIV-2, and SIVmac isolates, our analysis indicate that the genetic diversity of SIVagm is amazingly extensive. Therefore the proposed studies have two major goals. One is to continue search for SIVagm isolates that are closely related to HIV-1, HIV-2, or SIVmac. The other is to determine whether viral and /or host factors are important in pathogenesis and species specificity of these viruses. Additional SIVagm isolates will be obtained form African green monkeys from geographically dispersed regions of Africa. The viral isolates will be screened by gag-pol gene-specific probes. The ones closely related to HIV-1, HIV-2, or SIVagm isolates may lead us to identify the origin of lentiviruses that cause AIDS in humans. The pathogenic potential and species specificity of SIVagm and SIVmac will be examined in homologous and heterologous monkey species. These analyses will direct us to search for viral and /or host factors important for pathogenesis. If the viral factors prove to be important attempts will be made to locate pathogenic determinants by generating hybrid viruses; replacing genes or regions of the non-pathogenic strains with that of the pathogenic ones. If all attempts to establish viral factor being important to pathogenesis have failed then we may have to conclude that host factors are important. Attempts will then be made to identify differences in target cells, define host responses and other genetic factors in the hosts.